Ultra-Marathon-Induced Increase in Serum Levels of Vitamin D Metabolites: A Double-Blind Randomized Controlled Trial

Purpose: While an increasing number of studies demonstrate the importance of vitamin D for athletic performance, the effects of any type of exercise on vitamin D metabolism are poorly characterized. We aimed to identify the responses of some vitamin D metabolites to ultra-marathon runs. Methods: A repeated-measures design was implemented, in which 27 amateur runners were assigned into two groups: those who received a single dose of vitamin D₃ (150,000 IU) 24 h before the start of the marathon (n = 13) and those (n = 14) who received a placebo. Blood samples were collected 24 h before, immediately after, and 24 h after the run. Results: In both groups of runners, serum 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ levels significantly increased by 83%, 63%, and 182% after the ultra-marathon, respectively. The increase was most pronounced in the vitamin D group. Body mass and fat mass significantly decreased after the run in both groups. Conclusions: Ultra-marathon induces the mobilization of vitamin D into the blood. Furthermore, the 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ increases imply that the exercise stimulates vitamin D metabolism.     

Fasting and Exercise Induce Changes in Serum Vitamin D Metabolites in Healthy Men

Background: Vitamin D plays pleiotropic roles in the body and hence, changes in its metabolism and distribution during starvation could play an important role in the adaptive response to famine. We aimed to identify the responses of some vitamin D metabolites to 8 d of fasting and exercise. Methods: A repeated-measures design was implemented, in which 14 male volunteers fasted for 8 d and performed an exercise test before and after fasting. Serum samples were collected on day 1 after night fasting and after 8 d of complete food restriction, before and 1 h and 3 h after exercise. Results: After 8 d of fasting, compared with baseline values, serum 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ levels significantly increased; those of 25(OH)D₃ and 1,25(OH)₂D₃ were unaffected; and those of 25(OH)D₂ decreased. Exercise on the first day of fasting induced an increase in serum 3-epi-25(OH)D₃ levels, while exercise performed after 8 d of fasting induced an increase in 25(OH)D₃, 24,25(OH)₂D₃, 25(OH)D₂, and 3-epi-25(OH)D₃ levels. Conclusion: Increases in 24,25(OH)₂D₃ and 3-epi-25(OH)D₃ levels imply that fasting stimulates vitamin D metabolism. The effects of exercise on serum vitamin D metabolites, which are most pronounced after fasting and in subjects with serum 25(OH)D₃ above 25 ng/mL, support the notion that fasting and exercise augment vitamin D metabolism.     

Factors Associated with Serum Vitamin D Metabolites and Vitamin D Metabolite Ratios in Premenopausal Women

The most representative indicator of vitamin D status in clinical practice is 25(OH)D₃, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39–50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE–LC–MS/MS platform. The association between participant’s characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D₃ concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)₂D₃/25(OH)D₃) and a higher R4 (24,25(OH)₂D₃/1,25(OH)₂D₃) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D₃/Vit D₃) and R3 (24,25(OH)₂D₃/25(OH)D₃), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.     

Nordic Walking Rather Than High Intensity Interval Training Reduced Myostatin Concentration More Effectively in Elderly Subjects and the Range of This Drop Was Modified by Metabolites of Vitamin D

The COVID-19 pandemic and subsequent self-isolation exacerbated the problem of insufficient amounts of physical activity and its consequences. At the same time, this revealed the advantage of vitamin D. Thus, there was a need to verify the effects of those forms of training that can be performed independently. In this study, we examined the effects of Nordic walking (NW) and high intensity interval training (HIIT) with regard to the impact of the metabolite vitamin D. We assigned 32 overweight adults (age = 61 ± 12 years) to one of two training groups: NW = 18 and HIIT = 14. Body composition assessment and blood sample collection were conducted before starting the training programs and a day after their completion. NW training induced a significant decrease in myostatin (p = 0.05) concentration; however, the range was dependent on the baseline concentrations of vitamin D metabolites. This drop was accompanied by a significant negative correlation with the decorin concentration. Unexpectedly, NW caused a decrement in both forms of osteocalcin: undercarboxylated (Glu-OC) and carboxylated-type (Gla-OC). The scope of Glu-OC changes was dependent on a baseline concentration of 25(OH)D₂ (r = −0.60, p = 0.01). In contrast, the HIIT protocol did not induce any changes. Overall results revealed that NW diminished the myostatin concentration and that this effect is more pronounced among adults with a sufficient concentration of vitamin D metabolites.     

Vitamin D Metabolite Profile in Cholecalciferol- or Calcitriol-Supplemented Healthy and Mammary Gland Tumor-Bearing Mice

To analyze if the prometastatic activity of calcitriol (active vitamin D₃ metabolite), which was previously observed in a 4T1 breast cancer model, is also found in other breast cancers, and to assess the impact of various schemes of vitamin D supply, we used 4T1 and E0771 mouse metastatic and 67NR nonmetastatic cells in this study. BALB/c and C57BL/6 healthy and tumor-bearing mice were exposed to a control (1000 IU), low- (100 IU), and high- (5000 IU) vitamin D₃ diets. Additionally, from day 7 of tumor transplantation, the 1000 and 100 IU groups were gavaged with calcitriol (+cal). After 8 weeks of feeding, plasma levels of 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ were significantly lower in calcitriol-treated and vitamin D-deficient groups than in the control, whereas the levels of all metabolites were increased in the 5000 IU group. The ratio of 25(OH)D₃:24,25(OH)₂D₃ was increased in both calcitriol-treated groups, whereas the ratio of 25(OH)D₃:3-epi-25(OH)D₃ was increased only in the 100 IU group but decreased in the 5000 IU group. In contrast to E0771, 4T1 lung metastasis was accelerated in all vitamin D-supplemented mice, as well as in the deficient group with an increased inflammatory response. 67NR tumor growth was transiently inhibited in the 1000 IU+cal group, but single metastases were observed in the 5000 and 100 IU groups. Based on the results, we conclude that various schemes of vitamin D supply and vitamin D deficiency led to similar metabolite profiles irrespective of the mice strain and tumor burden. However, depending on the type of breast cancer, different effects on tumor growth and metastasis were noticed.     

Determination of vitamin D3 and 25-hydroxyvitamin D3 in foodstuffs by HPLC UV-DAD and LC–MS/MS

In order to generate new data for vitamin D content for the Canadian Nutrient File, a method for the quantification of vitamin D₃ and 25(OH)D₃ in foodstuffs has been modified and improved. Vitamin D₃ was quantified using reverse phase liquid chromatography (LC) with UV-diode array detector (UV-DAD), while 25(OH)D₃ was measured by triple quadrupole mass spectrometry (APCI MS/MS). Quantification was by internal standards (IS) using vitamin D₂ and 25(OH)D₂. A Certified Reference Material (CRM-421 containing vitamin D₃) and a control sample (internally generated reference material of ground pork containing both vitamin D₃ and 25(OH)D₃) were used as validation and quality control tools. Limit of detection for both compounds was 0.04 μg/100 g. Accuracy for vitamin D in the CRM-421 was 99% (0.142 mg/kg for a target of 0.143, n = 10). Recovery of vitamin D₃ in ground pork was 97% (88% absolute recovery). For 25(OH)D₃, a recovery of 94% (73% absolute recovery) was obtained. Using this method, data for vitamin D₃ and 25(OH)D₃ content in a variety of foods (pork, beef, eggs, poultry, fish, and dinners) have been generated.     

A new method for the determination of vitamin D3 and 25-hydroxyvitamin D3 in meat

The total vitamin D content in meat, i.e., vitamin D₃ and 25-hydroxyvitamin D₃, was determined by HPLC after alkaline hydrolysation, solid-phase extraction and semi-preparative HPLC. For detection, a DAD detector between 220 and 320 nm was used and quantification was performed at 265 nm. Vitamin D₂ was used as internal standard for vitamin D₃ as well as for 25-hydroxyvitamin D₃. Precision for vitamin D₃ was determined in lean meat and lard to 9.1% and 7.1%, respectively. The corresponding values for 25-hydroxyvitamin D₃ were 8.9% and 9.9%. Accuracy was determined in spiked samples, which showed a recovery of 94.7% and 99.0% for vitamin D₃ and 25-hydroxyvitamin D₃, respectively. The method is applicable for establishing data for food composition tables.     

Bariatric Surgery Induced Changes in Blood Cholesterol Are Modulated by Vitamin D Status

The effect of metabolically active bariatric surgery treatment on lipid metabolism is inconclusive. The authors of this study presume that initial vitamin D status may play a regulating role in influencing the beneficial post-effects of bariatric surgery, especially the lipid profile. The biochemical data obtained from 24 patients who had undergone laparoscopic one-anastomosis gastric bypass (OAGB) at baseline, 3 months before the surgery, at the time of surgery, and 6 months later, demonstrate that vitamin D status influenced the postoperative lipid profile. The baseline established the partition line which divided patients into two groups according to the stated calcidiol initial concentration level of 32 ng/mL. The data shows that OAGB induces a decrease in TG and hsCRP while increasing HDL. Conversely, in patients whose 25(OH)D₃ was below 32 ng/mL TC significantly increased while those above this concentration remained in the normal physiological range. The changes induced by OAGB in TG, glucose, and hsCRP were similar in both groups. Unexpectedly, the surgery did not affect vitamin D metabolites. In conclusion, the results of the study suggest that a higher concentration of serum 25(OH)D₃ may enhance the protective effects of OAGB.     

Intake of 25-Hydroxyvitamin D3 May Reduce the Severity of Upper Respiratory Tract Infection: Post hoc Analysis of a Randomized,Double-Blind,Placebo-Controlled,Parallel Group Comparison Study

To evaluate the effects of 25-hydroxyvitamin D₃ (25OHD) on symptoms at the onset of the upper respiratory tract infection (URTI) in subjects with insufficient or deficient serum 25-hydroxyvitamin D levels, we conducted a post hoc analysis of data from a randomized, placebo-controlled study; the subjects received 10 μg of 25OHD per day or a placebo for 16 weeks. The Wisconsin Upper Respiratory Symptom Survey-21 was used to determine URTI. The study endpoints included WURSS-21 scores, number of URTI events, and proportion of medication (antibiotics, antipyretic analgesics) usage. We found that the physical symptom scores for “Runny nose,” “Sneezing,” and “Head congestion” were significantly lower in the 25OHD group than in the placebo group; for all items except “Breathe easily, “the quality of life” scores were significantly improved in the 25OHD group. There was no significant difference in the number of URTI events or the proportion of medication use between the groups. Collectively, the findings of this study indicate that a sufficient 25OHD intake can reduce physical symptoms at the onset of upper respiratory tract infection, particularly nasal symptoms, and may improve the quality of life at the time of onset.     

Differences in the Concentration of Vitamin D Metabolites in Plasma Due to the Low-Carbohydrate-High-Fat Diet and the Eastern European Diet—A Pilot Study

Vitamin D deficiency is a global problem with many health consequences, and it is currently recommended to supplement vitamin D. Change of diet should also be considered to ensure adequate vitamin D in the human body. The aim of this study was to assess the concentration of vitamin D metabolites in two different groups: one group on the low-carbohydrate-high-fat (LCHF) diet and the other group on the Eastern European (EE) diet. In the first stage, 817 participants declaring traditional EE diet or LCHF diet were investigated. Nutrition (self-reported 3-day estimated food record) and basic anthropometric parameters were assessed. After extra screening, 67 participants on the EE diet and 41 on the LCHF diet were qualified for the second stage. Plasma 25-hydroxycholecalciferol (25(OH)D₃) and (25(OH)D₂) concentration was measured by the validated HPLC—MS/MS method. Plasma 25(OH)D₃ concentration was significantly higher in the group on the LCHF diet (34.9 ± 15.9 ng/mL) than in the group on the EE diet (22.6 ± 12.1 ng/mL). No statistical differences were observed in plasma 25(OH)D₂ concentration between the study groups (p > 0.05). Women had a higher plasma 25(OH)D₂ concentration than men regardless of diet type. The LCHF diet had a positive influence on plasma vitamin D concentration. However, long-term use of the LCHF diet remains contentious due to the high risk of cardiovascular disease. This study confirmed that the type of diet influences the concentration of vitamin D metabolites in the plasma.     

Association of Dietary Vitamin D Intake,Serum 25(OH)D3, 25(OH)D2 with Cognitive Performance in the Elderly

Background: As life expectancy increases, cognitive performance decline in the elderly has become one of the major global challenges. We aimed to evaluate the association of dietary vitamin D (VD), serum 25-hydroxyvitamin D3 (25(OH)D₃), 25-hydroxyvitamin D2 (25(OH)D₂), and total 25-hydroxyvitamin (25(OH)D) concentration with cognitive performance in older Americans. Methods: The data from the National Health and Nutrition Examination Survey (NHANES), 2011–2014 was used. The cognitive performance was assessed by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning sub-test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). A binary logistic regression model was applied to evaluate the association between VD and cognitive performance, and restricted cubic spline model was adopted to evaluate the dose–response relationship. Results: While comparing to the lowest dietary VD intake group, the multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the highest dietary VD intake group were 0.51 (0.36–0.72) for the Animal Fluency test score and 0.45 (0.31–0.66) for DSST score, respectively; and those of serum total 25(OH)D and 25(OH)D₃ concentration were 0.68 (0.47–0.97) and 0.62 (0.44–0.86) for DSST score. L-shaped relationships were identified for dietary VD intake, serum total 25(OH)D and 25(OH)D₃ concentration with cognition performance. The associations between dietary VD intake, serum total 25(OH)D and cognitive performance were non-significant when stratified by gender. Conclusions: The study indicates that dietary VD intake, serum total 25(OH)D and 25(OH)D₃ concentration were positively associated with cognitive performance. Further studies are needed to clarify the possible effects of dietary VD intake and serum 25(OH)D₂, 25(OH)D₃ on cognitive performance.     

血清25羟基维生素D_3对佝偻病早期诊断的研究

对82例佝偻病患儿与30例健康儿童用竞争蛋白结合法测定血清25羟基维生素D_3(25OHD_3),同时测定了血清钙(Ca~(2+))、磷(P~(3+)),碱性磷酸酶(ALP)。结果表明,佝偻病患儿血Ca~(2+)、P~(3+)、25(OH)D_3值降低,血ALP增高。佝偻病激期,血25(OH)D_3水平明显低于初期水平,恢复期上升,且初期、激期、恢复期三组间比较差异显著。相关分析显示,血25(OH)D_3与Ca~(2+)、P~(3+)无相关性,与ALP呈负相关性。以上结果表明血25(OH)D_3不仅可作为佝偻病的早期诊断指标之一,而且在佝偻病不同病期值变化不同,对判定佝偻病病期有极大的临床意义。     

1,25-(OH)2D3抑制人肝癌细胞增殖的研究

目的：探讨1，25－（OH）2D3抑制肝癌细胞增殖的机制。方法：体外培养肝癌细胞株SMMC－7721，培养基因10、50及100（nmol/L)1，25－（OH）2D3作用2d,4d,6d后，用四唑盐比色试验（MTT）和平板克隆形成实验检测细胞的存活和生长；台盼蓝拒染法绘制生长曲线；DNA凝胶电泳检测肝癌细胞凋亡。结果：MTT和平板克隆形成实验检测结果显示10－100nmol/L的1，25－（OH）2D3均对SMMC－7721细胞株有显的抑制作用，且呈剂量－效应关系。DNA凝胶电泳结果显示，1，25－（OH）2D3能够诱导SMMC－7721细胞凋亡。结论：1，25－（OH）2D3对于人肝癌细胞株SMMC－7721的增殖有显的抑制，其机理可能是通过干扰肝癌细胞的DNA代谢和诱导肝癌细胞凋亡。     

Relative Efficacy of Vitamin D2 and Vitamin D3 in Improving Vitamin D Status: Systematic Review and Meta-Analysis

Background: Widespread prevalence of vitamin D deficiency has been documented globally. Commonly used interventions to address this deficiency include supplementation and/or fortification with either ergocalciferol (vitamin D₂) or cholecalciferol (vitamin D₃), but the relative efficacy of these two vitamers is unclear. The current study aimed to evaluate the relative efficacy of ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃) for raising the serum levels of vitamin D metabolites and functional indicators including serum parathyroid (PTH) levels, isometric muscle strength, hand grip strength and bone mineral density. Methods: Randomized and non-randomized controlled studies evaluating relative efficacy of ergocalciferol and cholecalciferol were systematically reviewed to synthesize quantitative and qualitative evidence as per the recommendations of according to “Preferred Reporting Items for Systematic reviews and Meta-analysis” guidelines. Search terms were constructed on the basis of the “participants”, “intervention”, “control”, “outcome” and “study type” (PICOS) strategy to systematically search the popular electronic databases. Relevant data from studies meeting inclusion and exclusion criteria were extracted and analyzed. Meta-regression, subgroup and sensitivity analyses were performed to investigate the influence of study-level characteristics including intervention dosage, frequency of dosing, interval between the last dose and test for outcome assessment, participant characteristics and analytical methods. Results: Apparently healthy human participants (n = 1277) from 24 studies were included for meta-analysis. The quantitative analysis suggested higher efficacy of cholecalciferol than ergocalciferol in improving total 25(OH)D (mean difference: 15.69, 95%CI: 9.46 to 21.93 nmol/L) and reducing PTH levels, consistently across variable participant demographics, dosage and vehicle of supplementation. Meta-regression suggested smaller differences in the efficacy of cholecalciferol and ergocalciferol at lower doses. Average daily dose was the single significant predictor of effect size, as revealed by multivariate meta-regression analysis. Conclusions: Compared to ergocalciferol, cholecalciferol intervention was more efficacious in improving vitamin D status (serum levels of total 25(OH)D and 25(OH)D₃) and regulating PTH levels, irrespective of the participant demographics, dosage and vehicle of supplementation.     

The effect on the bones of condensed phosphate when used as food additives: Its Importance in Relation to Preventive Medicine

Based on the fact that chemical products such as binding agents are produced by mixing three kinds of phosphates with different ratios, we mixed metaphosphate, polyphosphate and pyrophosphate. Each was made to Na-phosphate, K-phosphate, and Ca-phosphate and each was mixed with commercial feeds so that the content of P would be approximately 0.1, 0.15, 0.3, 0.4, 0.6 and 1.0%. The prepared pellets were given to ICR, CF # 1 and AKR strains of mice at 29 days of age for 680 days and observations were made through this experimental period at different stages. The observations were also carried out on the mice administered with the experimental feeds for 1.5 months from 9 to 10.5 months of age. The observations were compared with those of the control group at all times. As a result, plasma 1 α, 25 (OH)₂ D₃ and P levels were always significantly higher in the phosphate administered groups relative to the control. Urine P and Fe increased while urine Ca decreased in the phosphate-treated groups. The effect of phosphates on the bones was studied taking soft X-ray pictures of hind legs and applying microdensitometry to them. Through these observations we recognized thinning of the cortex of bones, reduction of marrow trabecules and development of osteophyte. Histological observations disclosed that changes in knee joint tissues were apparent; that is, a decrease in or an irregular loss of the number of cells in superficial, intermediate, and radial strata of the joint cartilage, proliferation of subchondral bone, and the development of osteophytes were noted. As for muscles, diameters of musclar fibers became smaller; in particular, type II fibers showed greater shrinkage. Regarding kidneys, swelling and atrophy of glomerular capillaries, proliferation of mesangial cells, nephroselerosis, swelling, thinning, and loss of tubular epithelium, interstitial tissue inflammation, development of cylindruria, and deposition of calcium were observed. All these changes seem to be a particularly advanced aspect of the changes which are more pronounced with increasing dose and age. These changes were found even in the group administered with the feed containing 0.1% phosphorus, and, these changes were dependent on the concentration level of P. It was observed that administration to older subjects for a short term (1.5 months) produced effects stronger than those to younger subjects administered for a long term (10.5 months). The effects of condensed Ca-phosphate on bones were similar to those of condensed Na- and K-phosphates, and, hence, it was supposed that these effects were caused by phosphate radicals. An erratum to this article is available at .     

微量血25—（OH）D3及相关指标在婴幼儿佝偻病诊断中的评价

探讨婴幼儿维生素Ｄ缺乏性佝偻病的早期诊断。方法应用微量末稍血测定血清２５－（ＯＨ）Ｄ３和相关指标,对２４８名０－３岁儿童进行调查。结果２５－（ＯＨ）Ｄ３、ＡＬＰ、ＡＬＰ３无性别差异,在每半年一个龄龄组分组中,以０－６月龄组婴幼儿的２５－（ＯＨ）Ｄ３最低,而ＡＬＰ、ＡＬＰ明显升高。     

生长激素治疗前后GHD儿童维生素D变化的研究

【目的】探讨生长激素缺乏症(growth hormone deficiency,GHD)患儿、非GH缺乏性矮身材(non-GHdeficient short stature,NGHDSS)患儿及GHD患儿应用生长激素治疗3个月后的25-羟维生素D3[25-(OH)D3]、1,25-二羟维生素D3[1,25-(OH)2D3、]的变化。【方法】20例GHD患儿在治疗前及治疗3月后分别测血清25-(OH)D3、1,25-(OH)2D3水平并观察他们的身高变化,与20例NGHDSS患儿和20例正常儿童进行对照。放射免疫分析法测定血清25-(OH)D3、1,25-(OH)2D3水平。多组均数比较采用单因素方差分析,治疗前后均数间较采用配对t检验。【结果】GHD患儿治疗前血清25-(OH)D3水平低于正常对照组(P<0.05),治疗3个月后血清25-(OH)D3、1,25-(OH)2D3水平较治疗前增加(P值均<0.05),并高于对照组(P值均<0.05)。NGHDSS患儿血清25-(OH)D3水平高于GHD组(P<0.05),与正常对照组差异无显著性(P>0.05)。NGHDSS患儿血清1,25-(OH)2D3水平与正常对照组及GHD组差异均无显著性(两者P>0.05)。【结论】GHD患者血清25-(OH)D3低于正常,治疗后血清25-(OH)D3、1,25-(OH)2D3水平上升,推测GH通过直接或间接作用增强α羟化酶活性,促进维生素D的代谢。     

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

This is a narrative review of the evidence supporting vitamin D’s anticancer actions. The first section reviews the findings from ecological studies of cancer with respect to indices of solar radiation, which found a reduced risk of incidence and mortality for approximately 23 types of cancer. Meta-analyses of observational studies reported the inverse correlations of serum 25-hydroxyvitamin D [25(OH)D] with the incidence of 12 types of cancer. Case-control studies with a 25(OH)D concentration measured near the time of cancer diagnosis are stronger than nested case-control and cohort studies as long follow-up times reduce the correlations due to changes in 25(OH)D with time. There is no evidence that undiagnosed cancer reduces 25(OH)D concentrations unless the cancer is at a very advanced stage. Meta-analyses of cancer incidence with respect to dietary intake have had limited success due to the low amount of vitamin D in most diets. An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce cancer incidence rates by 70 ± 10%. Clinical trials have provided limited support for the UVB-vitamin D-cancer hypothesis due to poor design and execution. In recent decades, many experimental studies in cultured cells and animal models have described a wide range of anticancer effects of vitamin D compounds. This paper will review studies showing the inhibition of tumor cell proliferation, dedifferentiation, and invasion together with the sensitization to proapoptotic agents. Moreover, 1,25-(OH)₂D₃ and other vitamin D receptor agonists modulate the biology of several types of stromal cells such as fibroblasts, endothelial and immune cells in a way that interferes the apparition of metastases. In sum, the available mechanistic data support the global protective action of vitamin D against several important types of cancer.     

Vitamin D and Cardiovascular Disease

Vitamin D participates in numerous physiologic and pathologic processes. Most tissues have vitamin D receptors (VDRs), and vitamin D is an important regulator of gene expression. Approximately 1 billion people worldwide have insufficient levels of vitamin D. Deficiency has been associated with many chronic diseases, including cardiovascular disease (CVD), which is the leading cause of death in both men and women. A relationship between vitamin D and CVD is implicated; however studies show conflicting data. Epidemiologic evidence and observational studies demonstrate an association between vitamin D deficiency and CVD; however, this is not substantiated by randomized controlled trials (RCTs). Many questions remain unanswered, but growing evidence supports a beneficial role of vitamin D on cardiovascular health.

Key teaching points:

? Vitamin D influences many cellular functions.

? A global pandemic of vitamin D deficiency exists.

? Epidemiologic data and observational studies suggest that vitamin D deficiency may increase cardiovascular risk.

? RCTs show no significant relationship (however, studies have significant limitations).

? The association between vitamin D status and CVD is uncertain, but low vitamin D levels may be an independent and modifiable CV risk factor.